Endogenous tachykinins play a role in IL-1-induced neutrophil accumulation: involvement of NK-1 receptors.

Pretreatment of mice with capsaicin resulted in approximately 40% inhibition of the polymorphonuclear leucocyte (PMN) influx elicited by interleukin-1 (IL-1) injected into a murine air-pouch. This inhibition was mimicked by two selective antagonists of neurokinin-1 (NK-1) tachykinin (TK) receptors, i.e. CP-96,345 and RP-67,580, but not by the inactive enantiomer RP-68,651. A selective NK-2 antagonist, SR-48,968, was inactive. The natural peptide, substance P (SP), and a selective NK-1 agonist, (Sar9)SP, induced PMN infiltration into the murine air-pouch, whereas a selective NK-2 agonist, (beta Ala8)NK-A(4-10), was ineffective. Moreover, SP-induced PMN accumulation was prevented by co-administration of RP-67,580 and CP-96,345, but not by RP-68,651. These findings suggest that the release of an endogenous TK, possibly SP, may occur following IL-1 injection in vivo, indicating a contributory role for neuropeptides in the PMN migration elicited by this cytokine. The action of selective agonists and antagonists suggests the involvement of NK-1 receptors.